Elderly Myeloma Research Articles

Daratumumab Treatment for "Truly Frail" Elderly Myeloma Patients.

Remarkable advancements have been made in the treatment outcomes of multiple myeloma (MM) patients; however, for frail elderly patients, these treatment outcomes are still insufficient. Elderly MM patients are increasing, as are their treatment regimens. There is a heightened demand to assess these patients in order to provide optimized treatments. While continuous treatment is more common for MM patients when compared to fixed-duration treatment, due to the risk of treatment interruption causing reduced survival rates, effectiveness and safety are essential. Treatment goals vary for each patient, but must preserve their quality of life (QOL). When planning treatments for these patients, frailty evaluation is increasingly emphasized as a stratification factor which helps develop accurate screening tools. Daratumumab (DARA) therapy, used globally, is not only effective in frail elderly MM patients, but also has QOL benefits. Proficiency in utilizing DARA regimens is potentially advantageous for patients not included in clinical trials, and innovative usage can further broaden its scope. The development of tools to accurately assess frailty and the establishment of optimal treatments for frail elderly MM patients are imperative. This review is an overview, challenging the frailty assessments for MM patients, re-examining the evidence for DARA regimens in frail elderly MM patients, and discussing potential areas for improvement.

Daratumumab Bortezomib and Dexamethasone in Transplant Ineligible Newly Diagnosed Elderly Myeloma Patients - a Trial By Asian Myeloma Network

Background: Transplant ineligible (TI) newly diagnosed Multiple Myeloma (NDMM) patients have inferior outcomes compared to that of a transplant population. This led to investigation of therapies with novel mechanisms of action to improve outcomes in this group. MAIA and ALCYONE studies have showed impressive outcomes in this group of patients. However, significant toxicities are a concern when delivering multiple anti-myeloma drugs concurrently in a continuous schedule in elderly patients. In this context, the efficacy and safety of Daratumumab, Bortezomib (finite) and dexamethasone in NDMM remains unknown. Aims: In this study, we investigated the combination of Daratumumab Bortezomib (in a finite schedule), and dexamethasone (DVd) followed by Daratumumab as maintenance in transplant ineligible TI NDMM patients from Asia (NCT03695744). Methods: This is a prospective, open-label, single-arm, phase 2 study of TI NDMM patients conducted by Asian Myeloma Network across three hospitals in Singapore. The primary end point was overall response rate. Secondary end points included progression free survival, overall survival, toxicity & safety, duration of response, minimal residual disease (MRD) and sustained MRD negativity. The study was approved by SingHealth Centralised IRB (CIRB No 2018/2730). Patients with confirmed diagnosis of MM, fulfilling inclusion / exclusion criteria were enrolled after signing informed consent. Patients received IV daratumumab 16mg/kg weekly in weeks 1-9, Q3 weekly from weeks 10 to 24 and Q4 weekly from week 25 onwards. Subcutaneous Bortezomib 1.3mg/m 2 and Dexamethasone 40mg (20mg for patients >75 years old) once weekly were administered for 9 months, followed by daratumumab maintenance until progression or toxicity. Response assessments were as per IMWG criteria and serial QOL data was also collected. Regular safety reviews were performed from recruitment of first patient by an independent committee. Here we report the protocol specified interim analysis of safety and efficacy end points. Results: From Oct 2019 till Sep 2021, we enrolled 27 patients. Median age was 74.3 years (range 70.5 to 79.2 years; 13/27 patients were >75years). 13 male and 14 were female patients. Ethnic distribution was 20 Chinese, 3 Malay, 3 Indian and 1 Others. ECOG performance status was 0 in 5(19%), 1 in 16(59%) and 2 in 6(22%) patients respectively. 11(41%) and 6(22%) patients belonged to Stage II and III ISS respectively. 14(52%) patients had CrCl <60ml/Min. 26(96%) patients experienced any grade adverse event with 17 experiencing a grade 3/4 event. Most common adverse events were infections, gastrointestinal disorders, peripheral neuropathy, and infusion related reactions. All grade and grade 3/4 AEs were relatively low, particularly haematological, given the absence of drugs known to cause significant myelotoxicity. Detailed AEs and SAEs are tabulated in Table 1. Three patients have died, of which one was due to a treatment related infection, while two others were unrelated (1 - suicide secondary to known mental illness, 1 - accidental fall & cervical spine injury). At data cut off (15 Oct 2022), 26 out of 27 patients had a response with 4(14.8%) sCR, 3 (11.1%) CR, 14 (51.9%) VGPR and 5 (18.5%) PR (1 missing assessment) giving an ORR of 96.3%. Median duration on Daratumumab was 16.3 mos and Bortezomib was 8 mos. 6 patients (22.2%) have experienced disease progression. With a median follow-up of 17.6 months, the 18-month progression free survival and overall survival were 65.4% & 89% respectively (median PFS and OS not estimable). Follow-up is on-going and we aim to report long-term survival, FISH/ cytogenetic & MRD results, toxicity and QOL data in future. Conclusion: DVd with Bortezomib in a finite schedule and Daratumumab maintenance achieved highly efficacious responses in elderly TI NDMM. Though this is a small study, toxicity rates here compare favorably to that noted in larger Phase 3 studies with quadruplets (Alcyone) and continuous triplet regimen as in the MAIA study. Whilst using novel agents like CD38 monoclonals upfront clearly improves responses and survival, minimizing toxicities without compromising efficacy by careful limitation of long-term concurrent exposure to multiple anti-myeloma drugs in an elderly population could help improve safety and quality of life. DVd could be an effective alternative in some elderly TI NDMM patients.

P-117 A prognostic score based on age, eGFR (CKD-EPI), performance status and ultra-high-risk disease outperforms R2-ISS for elderly myeloma patients: an analysis of the Greek myeloma study group registry

P-117 A prognostic score based on age, eGFR (CKD-EPI), performance status and ultra-high-risk disease outperforms R2-ISS for elderly myeloma patients: an analysis of the Greek myeloma study group registry

Similar Benefits of High-Dose Melphalan Based Conditioning Regimens Followed By Autologous Hematopoietic Cell Transplantation in Elderly Myeloma Population Compared to the Younger Group: Single Center Experience

Background: Multiple myeloma (MM) remains an incurable plasma cell malignancy and predominantly affects elderly population with a median age at onset around 70 years. High-dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT) remains an important consolidative measures even in the era of novel agents including anti-CD38 antibodies. HCT in elderly patients is typically met with concerns for increased toxicity in this age group. Here, we evaluated our single center experience of autologous HCT in the elderly for the last decade. Methods: Clinical transplant data on MM patients who underwent HCT at Moffitt Cancer Center (MCC) were retrospectively reviewed. BMT Research Analysis Information Network (BRAIN) database was used for data query. The study population was limited to first autologous HCT for MM and receiving high-dose melphalan based conditioning regimens. Patients were divided into 3 groups based on their age at HCT: Age < 65 (n=1044), 65-69 (n=428), and 70+ (n=222). Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier method and compared with log-rank testing. Cumulative incidence function was compared with Gray's test. Results: There were 1694 MM patients who underwent autologous HCT with high-dose melphalan-based regimen at MCC from 2010 to 2021. Over 100 transplants per year were performed at our institution for MM since 2011 at both inpatient and outpatient settings. Median HCT-CI was 2, 3, and 3 for ages <65, 65-69, and 70+, respectively. Median serum creatinine (range) was 0.9 (0.5-10.1), 0.8 (0.4 - 11.9), and 0.9 (0.4 - 8.4) for ages <65, 65-69, and 70+, respectively. Reduced melphalan dosing (MEL140) was used in 5.6%, 10.1%, and 82.7% for ages <65, 65-69, and 70+, respectively. Univariate analysis showed that the 5-year OS for ages <65, 65-69, and 70+ was 71.1% (95% confidence interval (CI): 67.7-74.3), 69.6% (95%CI: 63.9-74.6), and 65.4% (95%CI: 56.4-73.0), respectively (Log rank, p=0.34, Figure). The 5-year PFS for ages <65, 65-69, and 70+ was 48.0% (95%CI: 44.3-51.5), 46.0% (95%CI: 40.0-51.8), and 46.0% (95%CI: 37.3-54.3), respectively (Log rank, p=0.64). The 5-year cumulative incidence of relapse for ages <65, 65-69, and 70+ was 44.9% (95%CI: 41.4-48.4), 44.4% (95%CI: 38.6-50.1), and 38.6% (95%CI: 31.1-46.0), respectively (Gray's test, p=0.2). The 3-moth, 1-year, and 5-year cumulative incidences of nonrelapse mortality (NRM) were 0.5% (95%CI: 0.2-1.2), 1.9% (95%CI: 1.2-2.9) and 7.0% (95%CI: 5.3-9.0) for age < 65, 0.7% (95%CI: 0.1-1.9), 0.9% (0.3-2.2%) and 9.4% (95%CI: 6.4-13.2) for ages 65-69, and 0.0% (95%CI: 0.0-0.0), 0.4% (95%CI: 0.0-2.4) and 15.2% (95%CI: 9.2-22.5) for age 70+, respectively, respectively (Gray's test, p=0.16). Additional multivariate analysis will be provided at the presentation. Conclusions: Overall, there were no differences in the MM HCT outcomes in different age groups at our center. Our data demonstrate the safe application of high-dose therapy in MM patients across the age group. Older MM patients appear to derive comparable survival benefits from HCT and should remain a standard consolidative measure. There is a suggestion that the NRM may be numerically higher in elderly population, and further analysis on long-term outcomes in elderly population is planned. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Prospective Single-Arm Study of Melphalan, Prednisolone and Lenalidomide (MPL) as First Line Treatment in Elderly Patients with Multiple Myeloma – An Institutional Study

Abstract Introduction Multiple myeloma in the elderly population is rising in India. Such frail transplant-ineligible patients are less frequently included in clinical trials. Moreover, novel agents are not accessible to everyone. Melphalan-based chemotherapy regimens are frequently used in elderly myeloma patients. Our study revisited the role of melphalan, prednisone, and lenalidomide (MPL) as front-line therapy in this subgroup of patients. Objective The aim of this study was to determine the response, tolerance, and outcome of MPL in elderly patients with newly diagnosed multiple myeloma. Materials and Methods This prospective study was conducted at the Department of Medical Oncology at a tertiary cancer center during January 2012 to September 2013. Newly diagnosed patients with multiple myeloma &gt;60 years who were transplant ineligible formed the study subjects. Eligible patients received oral melphalan 0.18 mg/kg from D1 to 4, prednisone 2 mg/kg from D1 to 4, and lenalidomide 10 mg from D1 to 21 q28 days. Patients who achieved complete response/very good partial response (CR/VGPR) after 6 cycles of MPL received maintenance with lenalidomide 10 mg from D1 to 21 q28 days (MPL-L) until progression or 1 year whichever was earlier. Quality of life was assessed using the Eq. 5D questionnaire. Results Out of 46 patients, 25 were males and 21 were females. Median age was 67 years (range: 60—83 years). Majority had immunoglobulin G myeloma, followed by immunoglobulin A subtype. The median quality of life score at baseline was 50 (range: 30–70). Forty patients completed six cycles of MPL. The main toxicity was grade 1 to 2 hematological. There were no treatment-related deaths. Twenty-two (55%) achieved CR, 5 (13%) achieved VGPR, 4 (10%) achieved partial response, 6 (15%) achieved stable disease, and 3 (7%) had progressive disease. Twenty-seven patients received lenalidomide maintenance. At a median follow-up of 55 months, the 2- and 5-year progression-free survival was 60 and 18%, respectively. The overall survival at 2 and 5 years were 80 and 53%, respectively. The median number of subsequent lines of treatment was 2 (range: 1–4). The quality of life was improved and preserved in all study subjects. At 8 years, three patients had second malignant neoplasms and seven are alive. Conclusion MPL-L is a well-tolerated and effective regimen in elderly myeloma with good overall response rates.

Conditioning with melphalan 200 mg/m2 and subsequent ASCT improves progression-free and overall survival in elderly myeloma patients compared to standard of care.

Despite the effectiveness of newer drugs for the treatment of multiple myeloma (MM), the outcomes are further improved by subsequent autologous stem cell transplantation (ASCT). Data on effectiveness in older patients are limited. We compared outcomes in patients aged 65-75 years depending on whether they were treated with ASCT or not and compared those to outcomes in patients <65 years. This was a retrospective, single-center study. We compared progression-free survival (PFS) and overall survival (OS) for all MM patients below and above the age of 65 years treated ± ASCT at the Karolinska University Hospital between 2010 and 2020. PFS and OS were calculated by the Kaplan-Meier method. Variables affecting PFS and OS were evaluated using Cox regression model. Both PFS and OS were improved in the group 65-75 years treated +ASCT compared to those treated pharmacologically (p=0.008 and p < 0.001, respectively). There were no significant differences between patients <65 years and those 65-75 years treated with ASCT. The findings indicate that even patients >65 years should be evaluated as candidates for ASCT. An individualized approach supported by a frailty/geriatric assessment score could assist clinicians to select the appropriate treatment for each patient.

Evaluation of the frailty characteristics and clinical outcomes according to the new frailty-based outcome prediction model (Myeloma Risk Profile-MRP) in a UK real-world cohort of elderly newly diagnosed Myeloma patients.

The management of myeloma in the elderly is shifting its focus towards reducing the risk of under-treating fit patients and the risk of over-treating frail patients. Frailty assessment is required in this patient group in order to individualise treatment decisions. In addition to the proven prognostic values of the International Myeloma Working Group (IMWG) frailty score and the revised Myeloma Co-morbidity Index (R-MCI), a new easy-to-use frailty-based risk profile score (high-risk (i.e. frail), medium risk (i.e. intermediate-fitness) and low-risk (i.e. fit)) named Myeloma Risk Profile (MRP) was shown to be predictive of survival in the clinical trial setting. In this retrospective real-world study, we set out to evaluate the frailty characteristics and clinical outcomes according to the different MRP scoring algorithm categories (frail vs. intermediate vs fit), in a high risk cohort of elderly newly diagnosed myeloma patients treated with the fixed-duration triplet therapy VCD (bortezomib with cyclophosphamide and dexamethasone). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Out of 100 patients, 62 were frail, 27 were intermediate and 11 were fit, according to MRP scores. To enable meaningful comparisons between comparable numbers, subgroups analyses for ORR, OS, PFS, and AEs focused on frail (n = 62) versus intermediate or fit (n = 38) patients. The proportion of patients in each subgroup who were able to complete the planned course of treatment was (frail: 43.5% vs. intermediate or fit: 55.3%). A higher proportion in the frail subgroup discontinued therapy due to progressive disease (19.4% vs. 2.6%). Discontinuation due to toxicity was comparable across subgroups (14.5% vs. 15.8%), ORR in the total cohort was 75%, and this was comparable between subgroups (frail: 74.2% vs. intermediate or fit: 76.3%). There was a trend for a shorter median OS in the frail subgroup but without a statistical significance: (frail vs. intermediate or fit): (46 months vs. not reached, HR: 1.94, 95% CI 0.89–4.2, p = 0.094). There was no difference in median PFS between subgroups: (frail vs. intermediate or fit): (11.8 vs. 9.9 months, HR: 0.99, 95% CI: 0.61–1.61, P = 0.982). This cohort demonstrated a higher incidence rate of AEs in frail patients compared to those in the intermediate or fit group: patients with at least one any grade toxicity (85.5% vs. 71.1%), patients with at least one ≥G3 AE (37.1% vs. 21.1%). In conclusion, our study is to the first to evaluate clinical outcomes according to MRP in a high risk real-world cohort of patients treated exclusively with the proteasome inhibitor-based VCD therapy. Our study demonstrated a trend for worse OS in addition to worse AE outcomes in the frail group, but no difference in PFS with this fixed-duration therapy. MRP is an easy-to-use tool in clinical practice; its prognostic value was validated in the real-world in a large cohort of patients from the Danish Registry. Further evaluation of MRP in the real-world when continuous therapies are used, can further support the generalisability of its prognostic value in elderly myeloma patients.

Review of End-of-Life Care and Supportive Care during Disease Course in Elderly Patients with Multiple Myeloma

BackgroundMultiple myeloma (MM) is a plasma cell malignancy of which the median age at diagnosis is 70 years old. The novel agents had contributed significant improvement in the overall survival of MM. However, there is a disparity in survival between young and old patients, and early mortality is high in patients older than 70. Therefore, before making a treatment plan for elderly MM patients, it is crucial to consider both quality of life and even end-of-life (EOL) care. This study evaluated EOL characteristics and real-world supportive care in elderly MM patients.MethodsWe retrospectively reviewed medical records of patients diagnosed with MM at an age older than 70 between January 2011 and April 2021. We identified baseline characteristics, symptom burdens, factors associated with hospitalizations during the disease course, and several indicators of EOL; place of death, length of hospitalization, cause of death, chief complaints, agreement of “do-not-resuscitate (DNR)”, other aggressive and less aggressive interventions in their last hospitalization.ResultA total of 52 patients were included. The median age at diagnosis is 76 years old. 12 (23.08%) patients showed initial Eastern cooperative oncology group (ECOG) performance status 3 or 4. 30 (57.69%) patients had hypertension, 18 (34.62%) had diabetes, and 8 (15.38%) had chronic lung disease; asthma, COPD, and bronchiectasis. 3 (5.77%) patients had initial International staging system (ISS) stage 1 disease, 16 (30.77%) had 2, and 29 (55.77%) had 3. Only 2 (3.85) patients never received chemotherapy; one of them showed initial ECOG 3, and the other was unknown. The median overall survival was 16.69 months.27 (51.92%) patients visited the emergency department during their disease course at least once, and 19 (36.54%) were admitted intensive care unit more than once. Only 4 (7.59%) patients were never admitted hospital during their disease course except for chemotherapy. The mean number of hospitalization was 3.23, and the reason for 41.67% of hospitalization was to control myeloma-related symptoms; general weakness, acute kidney injury, pain, fracture, cord compression, and anemia. The rate of hospitalization day after diagnosis was 9.85%.The EOL characteristics of 24 (46.15%) deceased at the hospital were analyzed. An average hospitalization length was 41.96 days. Other EOL characteristics are detailed in table 1.ConclusionElderly MM patients spent almost 10% of their disease duration at the hospital to control disease-related symptoms. It might explain why elderly MM patients received aggressive therapy despite their age and poor performance status. To enhance their quality of life, we need to focus more on supportive care and make a decision for chemotherapy carefully. Furthermore, for EOL care, discussion for performing an aggressive intervention with patients should be encouraged. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Randomized Study of Bortezomib, Cyclophosphamide and Dexamethasone Induction (VCD) Versus VCD and Daratumumab Induction Followed By Daratumumab Maintenance (VCDD) for the Initial Treatment of Transplant-Ineligible Patients with Multiple Myeloma (AMaRC 03-16)

A Randomized Study of Bortezomib, Cyclophosphamide and Dexamethasone Induction (VCD) Versus VCD and Daratumumab Induction Followed By Daratumumab Maintenance (VCDD) for the Initial Treatment of Transplant-Ineligible Patients with Multiple Myeloma (AMaRC 03-16)

Benefits of Autologous Stem Cell Transplantation for Elderly Myeloma Patients in the Last Quarter of Life

Although survival outcomes have improved dramatically over the last few decades in newly diagnosed myeloma patients, elderly patients have not yielded the same magnitude of benefit as evidenced by higher rates of reported myeloma-related deaths in patients over the age of 75. This is of particular importance given this cohort comprises a large proportion of myeloma patients with the median age of diagnosis being 70 years. One contributor to this discrepancy is reduced use of high-dose therapy and autologous stem cell transplantation (HDT/ASCT) in this population because of concerns for increased toxicity and safety. The objective of this retrospective analysis is to evaluate survival and safety outcomes in 53 newly diagnosed patients ≥74 years of age who underwent HDT/ASCT at our institution in comparison to 122 control patients in the same age bracket who did not undergo stem cell transplantation during this same time period. Patients treated at our institution were identified in our institutional myeloma database by age. They were all treated between November 2006 and October 2016 at the Winship Cancer Institute of Emory University. Fifty-three patients were identified who had undergone HDT/ASCT, and, to assess the relative benefit of ASCT, 122 control patients in the same age range were also identified who did not undergo HDT/ASCT during the same time period. The median age for the entire cohort was 77 years (74 years in the ASCT group versus 78 in the non-ASCT group). Median time to ASCT was 6 months (range 2-57 months). There were no gender or race differences between the 2 groups, although a higher proportion of high-risk patients underwent HDT/ASCT. Ninety-three percent of ASCT patients received triplet induction therapy with a proteasome inhibitor and immunomodulatory agent backbone in comparison to only 55% of patients the non-ASCT group. The median progression-free survival (PFS) for the ASCT group was 50 months versus 30 months in the non-ASCT group. The median overall survival (OS) was 80 months versus 40 months, respectively. In high-risk patients, the median PFS was 60.8 months, and the median OS was 77.8 months in the ASCT group compared to 26 months and 38 months in the non-ASCT group, respectively. There were no transplant-related deaths within the first 100 days in the ASCT group. This study offers real-world perspective and data on the safety and survival benefit of ASCT in the elderly population with a near doubling of OS when compared to those treated with similar regimens and modern agents without ASCT. These data provide a rationale for offering ASCT in elderly patients pending a thorough pretransplantation evaluation.

P-167: Real-world elderly myeloma patients: improved survival despite more adverse risk factors than younger patients and RCT populations. A study on behalf of the Nordic Myeloma Study Group

<h3>Background</h3> Elderly multiple myeloma (MM) patients are underrepresented in randomized clinical trials (RCTs). Prospective registries provide insight into real-world patient characteristics, treatment and outcome. The Danish Multiple Myeloma Registry (DMMR) and the Swedish Myeloma Registry (SMR), established in 2005 and 2008 respectively, are nationwide prospective registries with near 100% coverage. <h3>Methods</h3> We describe baseline characteristics, treatment and survival for patients diagnosed with active myeloma in the DMMR January 1st 2005-February 18th 2020, and the SMR January 1st 2008-December 31st 2019. We performed a retrospective comparison of patients aged ≥75 years at diagnosis to MM patients <75 years. Further, we compared our cohort to the populations in pivotal RCTs guiding the treatment of elderly myeloma patients. <h3>Results</h3> In total, we report on 4647 Swedish and Danish MM patients ≥75 years at diagnosis compared with MM patients <75 years (n=7378). Out of 4691 newly diagnosed MM patients in the DMMR, 36% (n=1688) were ≥75 years. Among 7334 MM patients in the SMR, 40% (n=2959) were ≥75 years. The elderly cohort presented with more advanced disease (46% ISS III in both registries vs 30.3% (SMR) and 34.6% (DMMR) among the younger cohorts). The proportion of patients with anemia and/or renal failure was higher in the older cohort. In comparison, important RCTs underpinning current treatment guidelines included a lower proportion of elderly patients and patients with ISS III. 30% of patients in the VISTA-trial (VMP vs MP) and the ALCYONE-trial (Dara-VMP vs VMP) were ≥75 years. In the FIRST trial (Rd continuously vs Rd 18 months vs MPT) 35% of patients were >75 years, while the MAIA trial (Dara-Rd vs Rd) has the largest proportion of elderly patients among these studies (43.6%). However, in the MAIA trial only 29% of patients presented with ISS III, compared to 46% of patients ≥75 years in our real-world population. Similarly, 35% of patients in VISTA and 38% in ALCYONE had ISS III. The FIRST trial had a composition more similar to the Swedish and Danish registry population with 35% of patients >75 years, and 48% of these patients with ISS stage III. The treatment strategies in the elderly were similar in Denmark and Sweden. Melphalan and prednisolone (MP) were replaced by bortezomib-based regimes from around 2012, while lenalidomide-based treatment increased in recent years. Median relative survival (RS) for patients ≥75 years in Denmark increased from 25 months to 36 months for patients diagnosed 2005-2007 and 2015-2016, respectively. Similarly, in Sweden the median RS increased from 24 months to 42 months for patients ≥75 years diagnosed 2008-2009 and 2016-2017, respectively. <h3>Conclusion</h3> The real-world MM population is older and has a higher proportion of patients with ISS III disease than patients included in the pivotal RCTs, and compared to the younger patient cohort. Future studies in MM patients should take this into account.

MM-254: Autologous Hematopoietic Stem Cell Transplantation in Elderly Patients with Multiple Myeloma as a Standard Therapeutic Procedure. Is it Feasible? Single Center Experience

Context Autologous peripheral blood stem cell transplant (PBSCT) ideally should be performed in every myeloma patient, but in the elderly, the procedure might be risky because of comorbidities, and the possibility of the organism to fully compensate possible complications. Objective Our main goal was to show that the age limit for autologous PBSCT in myeloma patients can be safely shifted upwards. Design We used conditioning with melphalan, followed by autologous PBSCT for elderly patients with myeloma, using the age limit of 65 years. Setting All patients were transplanted in the bone marrow transplant unit in the University Clinic for Hematology Skopje. They underwent standard post-transplant preventive and prophylactic measures during the period of pancytopenia. Patients or Other Participants We have done a retrospective analysis of patients with MM where autologous SCT was done. The main inclusion criteria was the diagnosis, age over 65, acceptable comorbidity profile. Interventions Mobilizing and harvesting of stem cells, melphalan conditioning, and application of the graft via central venous catheter were standard for all patients. Main Outcomes Measures We evaluated the rates of transplant related mortality (TRM), post-transplant follow-up, complete remission (CR). Results Our analysis of data for 20 years shows that we performed autologous PBSCT on 25 patients with myeloma at the age of 65 or older. 17 males (68%) and 8 female (32%). Average age was 67 years (65-73). All patients received melphalan conditioning. In 23 of the patients, we used non-cryopreserved hematopoietic stem cells. In two patients we performed tandem autologous PBSCT with no major complications. 75% had HTA, 20% some level of cardiomyopathy, 48% diabetes, and 12% with inserted prosthetic aortic valves. Our oldest patient was 73 years old and was still alive 2 years posttransplant. Our transplant related mortality was 0%. Conclusions Autologous PBSCT in elderly myeloma patients can be safe and effective, with careful selection of patients, balancing the risk profile of the patient, and the benefit of the procedure. Affective supportive care, monitoring, and reducing the risk of complications is an imperative to a good result. Autologous peripheral blood stem cell transplant (PBSCT) ideally should be performed in every myeloma patient, but in the elderly, the procedure might be risky because of comorbidities, and the possibility of the organism to fully compensate possible complications. Our main goal was to show that the age limit for autologous PBSCT in myeloma patients can be safely shifted upwards. We used conditioning with melphalan, followed by autologous PBSCT for elderly patients with myeloma, using the age limit of 65 years. All patients were transplanted in the bone marrow transplant unit in the University Clinic for Hematology Skopje. They underwent standard post-transplant preventive and prophylactic measures during the period of pancytopenia. We have done a retrospective analysis of patients with MM where autologous SCT was done. The main inclusion criteria was the diagnosis, age over 65, acceptable comorbidity profile. Mobilizing and harvesting of stem cells, melphalan conditioning, and application of the graft via central venous catheter were standard for all patients. We evaluated the rates of transplant related mortality (TRM), post-transplant follow-up, complete remission (CR). Our analysis of data for 20 years shows that we performed autologous PBSCT on 25 patients with myeloma at the age of 65 or older. 17 males (68%) and 8 female (32%). Average age was 67 years (65-73). All patients received melphalan conditioning. In 23 of the patients, we used non-cryopreserved hematopoietic stem cells. In two patients we performed tandem autologous PBSCT with no major complications. 75% had HTA, 20% some level of cardiomyopathy, 48% diabetes, and 12% with inserted prosthetic aortic valves. Our oldest patient was 73 years old and was still alive 2 years posttransplant. Our transplant related mortality was 0%. Autologous PBSCT in elderly myeloma patients can be safe and effective, with careful selection of patients, balancing the risk profile of the patient, and the benefit of the procedure. Affective supportive care, monitoring, and reducing the risk of complications is an imperative to a good result.

Age Is Not Important for Autologous Peripheral Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Introduction: High-dose melphalan followed by autologous hematopoietic cell transplantation (auto HSCT) has become the standard procedure for patients with symptomatic multiple myeloma (MM). Retrospective analyses suggest that the benefit of HDT extends to elderly myeloma patients, which is an important finding considering that the median age at diagnosis is 69 years (range: 65-74) for MM in United States, using 2010-2014 US SEER data. The aim of our study was to determine the effect of age on stem cell collection and engraftment in patients with MM.Materyal and Methods: From January 2010 through April 2016, data from 260 myeloma patients below the age of 65 were compared to 41 myeloma patients above 65 years of age who were eligible for auto HSCT according to geriatric assessment (GA), depending on the results of IMWG report in 2015. All these data were obtained from the Ankara University Faculty of Medicine Center for Therapeutic Apheresis and written informed consent was signed according to our institution regulations. Mostly bortezomib based regimens were given as induction therapy to our patients. Ninety two percent of the patients received only GCSF at a dose of 5 µg/kg BW twice-daily s.c. until stem cell procurement. Patients underwent further PBSC collections until we obtained the target dose >20 CD34+ cells/µL blood. A maximum of 3 collections were performed in the first mobilization; if the cell dose was not achieved, we submitted patients to a second mobilization.Results: Forty-one of 301 patients were above 65 years of age (median age 68, range 65-75) and 260 patients were below the age of 65 (median age 56, range 29-64). Baseline characteristics of the older and younger patient cohorts are summarized in Table-1. The median follow-up was 48.5 months (range 1-90) for age <65 years old patients and 46 months (range 1-90) for age ≥65 years old patients. Mobilization regimens for the younger patient population were G-CSF only (n:241), cyclophosphamide based (n:12) and +plerixafor (n:7). Mobilization in the older population was with cyclophosphamide based (n:4), G-CSF only (n:36) and +plerixafor (n=1) in whom poor mobilization had been predicted. The chemotherapy regimens were not statistically different between both age groups (chi square p value 0.37). There were no significant statistical differences in time from diagnosis to mobilization, number of prior therapies or disease status between both patient groups. The number of CD34-positive circulating cells before scheduled leukapheresis was mean 23.26 cells/μL in all patients (including patients who failed mobilization). Neutrophil engraftment was seen faster in elderly group (mean 10.4±3.1 vs. 11.5±1.8; p=0.008) but platelet engraftment was similar compared the younger patients with older ones (Table-2). In The probability of 5-year progression free survival (PFS) and overall survival (OS) in elderly patients with ISS-3 was 82.4%±12.1% and 48.5±16.5%. No statistical significance was observed for mean estimated 5-year OS in terms of patient age (<65 and ≥65 years; 82.5%±2.8% and 74.3%±8.7% p=0.29) (Figure-1). Less relapse was occurred in elderly cohort (17.5% vs. 35.4%) but the number of patients in this group does not provide enough statistical power to confirm whether the differences in PFS were statistically significant.Conclusion: To date, accepted approach for elderly patients with MM is not only improving survival, also their quality of life. Based on this single center study, auto-HSCT is safe and efficient in the treatment of elderly myeloma patients but no statistical difference was demonstrated in respect to age groups. [Display omitted] DisclosuresIlhan:Novartis: Consultancy.

Autologous Stem Cell Transplantation in Multiple Myeloma Patients Over 60 Years Old

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and p&lt;0.00, respectively). Our study indicated that a high dose (200 mg/m2 ) melphalan could safely be used in the physically fit patients at the ages of 60-69, and a reduced amount (140 mg/m2 ) would be the appropriate dose for the patients over 70. The quantity of infused CD34+ stem cells affect elderly MM patients; mobilization dynamics are also important factors for elderly myeloma. Age itself should not consider a barrier to ASCT, and a comprehensive geriatric evaluation should perform on elderly patients

Autologous Stem Cell Transplantation in Multiple Myeloma Patients Over 60 Years Old

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and p&lt;0.00, respectively). Our study indicated that a high dose (200 mg/m2 ) melphalan could safely be used in the physically fit patients at the ages of 60-69, and a reduced amount (140 mg/m2 ) would be the appropriate dose for the patients over 70. The quantity of infused CD34+ stem cells affect elderly MM patients; mobilization dynamics are also important factors for elderly myeloma. Age itself should not consider a barrier to ASCT, and a comprehensive geriatric evaluation should perform on elderly patients

A Randomized Study of Bortezomib, Cyclophosphamide and Dexamethasone Induction (VCD) Versus VCD and Daratumumab Induction Followed By Daratumumab Maintenance (VCDD) for the Initial Treatment of Transplant-Ineligible Patients with Multiple Myeloma (AMaRC 03-16)

A Randomized Study of Bortezomib, Cyclophosphamide and Dexamethasone Induction (VCD) Versus VCD and Daratumumab Induction Followed By Daratumumab Maintenance (VCDD) for the Initial Treatment of Transplant-Ineligible Patients with Multiple Myeloma (AMaRC 03-16)

Caring for older adults with multiple myeloma during the COVID-19 Pandemic: Perspective from the International Forum for Optimizing Care of Older Adults with Myeloma

The novel coronavirus (SARS-CoV-2, COVID-19) was first identified in the province of Wuhan, China in December 2019 [1], following the emergence of new cases of pneumonia of unknown etiology. Since then, the manifestations of COVID-19 infections have ranged from asymptomatic to severe respiratory infections, with increased morbidity in older adults including those with co-morbidities and cancer [2,3]. Presently, global mortality is reported at 4.7%, but this varies widely by location, from 0.7% in Germany to 10.8% in Italy [4]. As of April 13, 2020, the number of infections continues to rise well beyond the 1.9 million cases, and approximately 120,000 COVID-19-related deaths that have already occurred globally [5]. Multiple myeloma (MM) is a malignant plasma cell dyscrasia which predominantly affects older and often frail adults. Although tremendous gains have been made for older adults with MM, infections, including respiratory infections, significantly impact the rate of early mortality in these patients [6,7]. Furthermore, older adults with MM have age-associated vulnerabilities leading to heterogeneity in outcomes [8]. The complexity of caring for older patients have increased substantially during this pandemic, due to concern about their risk of severe morbidity of COVID19 infection. Optimal strategies for these patients will involve staging the malignancy/aging, while simultaneously considering the local prevalence of COVID-19 infection. Herein, we discuss strategies for the risk reduction of COVID-19 transmission, treatment stratification of anti-myeloma therapy and discussion regarding goals of care for older adults with MM during the COVID-19 pandemic.

The Spectrum of Exomic Mutation in Elderly Myeloma Differs Substantially from Patients at Younger Ages Consistent with a Different Evolutionary Trajectory to Full Blown Disease Based on Age of Onset

Background: An ever improving understanding of the heterogeneity in clinical behavior of multiple myeloma (MM) in older populations supports frailty-adapted therapy as a potential treatment approach. A deeper understanding of the evolutionary trajectory leading to full blown disease in elderly compared to younger patients may give insights into the interplay between mutations and frailty, allowing us to optimize therapy for this group. Methods: We analyzed next generation sequencing data from the Myeloma Genome Project (MGP) (n = 1273, mean age = 65) determining single nucleotide variants (SNV), copy number alterations (CNAs), and mutational signatures to determine age associated patterns. An initial analysis compared a population diagnosed older than age 75 (elderly patients, n = 232, mean age = 80 yrs) in comparison to a group diagnosed at age ≤ 74 (n = 1041, mean age = 62 yrs) and a younger subgroup of patients diagnosed at age ≤ 65 (n = 632, mean age = 57 yrs). Using RNASeq from the same dataset, we will analyze expression of TERT and other shelterin genes in an attempt to correlate changes to age, ATRX mutations, genomic instability, NHEJ, and telomere length as estimated using Telomere Hunter and TelSeq. The aim of this latter analysis being to highlight the importance of telomere biology in determining mutation patterns in the elderly population. Results: We identified age associated patterns in the distribution of mutations with patients age &gt; 74 yrs, when compared to all younger patients showing a significantly greater proportion of SNVs or indels in DIS3 (14.2% vs 8.7%, p = 0.005), HIST1H1E (5.6% vs 3.3%, p = 0.044), and IRF4 (5.6% vs 2.4%, p = 0.005). There were fewer SNVs and indels in CDKN1B (0% vs 1.3%, p = 0.038), FAM46C (6.5% vs 9.7%, p = 0.043), HUWE1 (1.7% vs 6.1%, p = 0.004) and SP140 (0.4% vs 2.9%, p = 0.014). In addition the elderly patient population was found to have proportionally more copy number gains at 1q21: CKS1B (47.4% vs 40.7%, p = 0.031), 5q23: TNFAIP8 (58.2% vs 50.0%, p = 0.012), 5p15: ADCY2 (58.2% vs 50.4%, p =0.016), 6p21: TNXB (39.2% vs 31.4%, p= 0.011), and 17q22: AKAP1 (30.2% vs 23.9%, p = 0.035) along with copy number losses at 16q: CYLD (38.8% vs 32.6%, p = 0.035), 6q25: PARK2 (40.5% vs 33.9% p = 0.028) and 2p23: DNMT3A (28.4% vs 23.0% p = 0.038). A greater proportion of elderly patients exhibited MYC tandem duplications (9.0% vs 5.6%, p = 0.032) while fewer elderly patients harbored MYC translocations (26.2% vs 19.3%, p = 0.015). These differences were further enhanced in comparisons to patients presenting under the age of 65, with elderly patients exhibiting fewer t(4;14) translocations (9.1% vs 14.4%, p = 0.019). Recent data has shown a significant time delay between MM initiation and disease presentation, and mutational signatures have been defined at varying evolutionary trajectories. We have examined if these signatures are different in elderly compared to younger cases. We could not identify a difference in the APOBEC mutational signature between any of the age-based series. We will present further analysis of other signatures and the role of telomere length at the meeting. Conclusions: Our results show significant differences in the genetic alterations between older and younger myeloma patients. These difference may lead to important differences in clinical behavior. The findings suggest disease behavior in the elderly may be driven relatively more frequently by acquired copy number alterations occurring over a period of long disease latency. Ongoing analysis is determining the prognostic impact of mutations in different age strata, which mutational signatures are driving these differences and how these impact clonal structure in the older populations. These results suggest that it should be possible to integrate genetic data and frailty-adaptive risk models to aid in the treatment of multiple myeloma that presents late in life. Disclosures Boyle: Amgen, Janssen, Takeda, Celgene Corporation: Other: Travel expenses; Amgen, Abbvie, Janssen, Takeda, Celgene Corporation: Honoraria. Davies:Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor; Janssen, Celgene: Other: Research Grant, Research Funding. Walker:Celgene: Research Funding. Flynt:Celgene Corporation: Employment, Equity Ownership. Thakurta:Celgene: Employment, Equity Ownership. Morgan:Celgene: Other: research grant, Research Funding; Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Impact of Combining Frailty Assessment Systems to Select Elderly Myeloma Patients Eligible for Autologous Peripheral Blood Stem Cell Transplantation

Introduction The International Myeloma Working Group (IMWG)-frailty index (IMWG-FI) and revised myeloma comorbidity index (R-MCI) are multiple myeloma (MM)-specific frailty scoring systems, which the European Myeloma Network advocates to assess patient frailty, and to select goals and treatments including autologous stem cell therapy (ASCT). In Japan, patients &lt;65 years old are recommended to receive ASCT under the guidelines of the Japanese Society of Hematology, The Japan Society for Hematopoietic Cell Transplantation, and Japanese Society of Myeloma. However, some Japanese institutes perform ASCTs on MM patients ≥65 years old, although the eligibility criteria and the ASCT methods are variable, or depending on the attending physicians' experience and preference, and doctor-patient relationships. In our institute, 17 MM patients ≥65 years old received ASCT and their frailty at the time of ASCT was retrospectively analyzed. Methods We performed 51 ASCTs on 43 MM patients between April 2017 and June 2019. Seventeen patients were elderly, and 34 were younger. The conditioning regimens were melphalan 200 mg/m2 for younger and 140 mg/m2 for the elderly patients. Both groups received the same supportive therapy. Frailty was compared using the IMWG-FI, R-MCI, and Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), and the toxicity and efficacy of ASCT were retrospectively analyzed. Results The patients' ages at the time of ASCT were statistically different between groups (67.8 vs 57.8 years old, p&lt;0.001). The number of fit and intermediate-fit patients by IMWG-FI were 14 and 3 in the elderly group, and 28 and 6 in the younger group, respectively (p=1.0). Fit and intermediate-fit patients by R-MCI were 13 and 4 in the elderly group, and 27 and 7 in the younger group, respectively (p=1.0) (Table 1). No patients were classified as frail in either group by the IMWG-FI and R-MCI. The median scores (ranges) of HCT-CI were 1 (0-5) in the elderly group, and 1.5 (0-5) in the younger group (p=0.93). The number of CD34 positive cells harvested from peripheral blood was lower in the elderly than in the younger group (3.8 vs 5.4×106/kg, p=0.0027). For the elderly and younger groups, the infused CD34 positive cell count (2.4×106 vs 2.4×106/kg, p=0.87), days for neutrophil (11 vs 11 days, p=0.87) and platelet engraftments (15 vs 15 days, p=0.7), and the hospitalization periods (26 vs 27 days, p=0.27) were not statistically different. Both groups had no transplantation-related deaths, similar rates of the non-hematologic adverse events (grade ≥3), an improvement in response (≥very good partial response (VGPR); 49% vs 74%, p=0.003) before vs after ASCT. Post-ASCT ≥VGPR rates were similar between the elderly and younger groups (73% vs 75%, p=1.0). Discussion We safely performed ASCT for elderly MM patients. The frailty status of the younger and elderly groups were the same, as evaluated by the IMWG-FI, R-MCI, and HCT-CI. Our eligibility criteria for MM patients for ASCT was by biological and not chronological age. Thus, the prospective assessment of elderly MM patients by these tools may enable us to evaluate the risks of elderly ASCT, through which elderly ASCT-eligible cases can be selected. Eleven of the 17 elderly patients were termed fit by the IMWG-FI and R-MCI, and scored 0-3 by HCT-CI, 6 of whom were 0-1. Five patients were intermediate-fit by either IMWG-FI or R-MCI, with 0-3 by HCT-CI. Only 1 patient was intermediate-Fit by both IMWG-FI and R-CMI, and was 5 by HCT-CI (Table 1). Based on our data, we propose a stratification system that can determine ASCT eligibility in elderly MM patients. The elderly patients regarded fit by IMWG-FI and R-MCI with 0-1 by HCT-CI could be stratified as Low Risk for elderly ASCT. In addition, the frail patients by IMWG-FI or R-MCI or &gt;3 by HCT-CI could be stratified as High Risk ineligible for elderly ASCT. Other patients could be Intermediate-Risk for elderly ASCT. Further studies are needed to determine the adequate melphalan dosage such as 200 mg/m2 for 65-69 year-old patients, and 140 mg/m2 for 70- Conclusion We retrospectively analyzed the elderly patients receiving ASCT using two MM-specific frailty indices and HCT-CI. We propose a new stratification system to select elderly patients eligible for ASCT. ASCT issues for the elderly MM patients should be examined prospectively. Disclosures No relevant conflicts of interest to declare.

Advancements in Treatment for Newly Diagnosed Frail and Elderly Myeloma Patients: A Systematic Review

Introduction: About 60% newly diagnosed multiple myeloma (NDMM) cases are above age of 60 years. The paucity of studies exclusively targeting management of frail patients has led to persistence of therapeutic uncertainties. With data on more than ten thousand patients, purpose of this review is to summarize the available therapeutic options with emphasis on recent advances for treatment of frail and elderly, transplant ineligible NDMM patients. Methods: We performed a comprehensive literature search on June 1st, 2019 on PubMed, Cochrane Library and ClinicalTrials.gov. We used the MeSH terms: 'Multiple Myeloma' and 'Frail Elderly', with associated entry words. Search yielded 71 studies regarding our topic of interest. Following PRISMA guidelines and subsequent screening by two reviewers, we shortlisted 19 ongoing/completed studies (n=10297) and included data from these studies in our systematic review. Results: Two/Three Drug regimens: Among the two drug regimens [Table 1], Lenalidomide (R) and Dexamethasone (D) (RD) combination has been most widely studied (n=1445). RD yielded objective response rate (ORR) of 81.3%, complete response (CR) or above of 24.9% and progression free survival (PFS) of 31.9 months in a phase III trial (Usmani, 2019) (n=369). Facon et al. (2019) [n=368] used Daratumumab (Dara)+R+D (DaraRD) which exhibited the best response overall with an ORR of 92.9%, CR of 47.6%, VGPR of 31.8% while the PFS was not reached till study end point. However, &gt;grade 3 neutropenia developed in 50% patients. Three-drug regimen of Bortezomib(V)+Melphalan(M)+Prednisolone(P) (VMP) has been the most widely studied regimen (n=1059) in four phase II/III clinical trials. In a phase II trial (Kizaki, 2016) (n=87), VMP yielded a PFS of 36 months and CR of 25%. In a Phase II trial by Larocca et al (2016, n=148), 3 cohorts (VP, V+ Cyclophosphamide (C) +P and VMP respectively) were studied. Best response was achieved by VMP with ORR of 86%, PFS of 17.1 months and CR of 14%, compared with VCP (ORR=67%, PFS=15.2 months and CR=2%) and VP (ORR=64%, PFS=14 months, CR=8%). However, the discontinuation rate (DR) due to AEs for VMP was relatively high (20%). A phase III trial (San-Miguel, 2018) (n=955) compared Carfilzomib(K)+M+P (KMP) against VMP. Median PFS was found to be 22.3 months with KMP Vs 22.1 months with VMP. Grade ≥3 AE rates were 74.7% for KMP and 76.2% for VMP. Thus, the results showed no significant difference between both regimens. Thalidomide (T) has also been used in three drug combinations in two phase II/III trials (n=667). Ixazomib(I)+T+D (ITD) in a phase II trial (Abildgaard, 2017) (n=120) revealed an ORR of 75% compared to ORR of 62% in a phase III trial (Benboubker et al, 2014) (n=547) using MPT. Notable &gt;grade 3 AEs with ITD were infections (15%) and cardiac abnormalities (10%) while with MPT were &gt;grade 3 neutropenia (45%) and infections (17%). A retrospective analysis by Facon et al. (2015, n=1517) comparing RD Vs MPT demonstrated that RD reduced the risk of progression or death by 21% compared to MPT in frail patients. 2. Four Drug Regimens: Four drug regimens have also been used in transplant-ineligible patients in two phase II/III trials (n=583). Mateos et al. (2015, n=233) conducted a phase II trial in which patients were treated with VMP+RD (VMPRD). 49 frail patients based on Age &gt;80 years (IMWG criteria) had ORR of 68%, PFS of 25 months and CR of 10%, with a DR of 63% due to toxicity or informed consent withdrawal. However, in the ALCYONE trial (San-Miguel, 2017) (n=350), use of Dara+VMP (DaraVMP) resulted in ORR of 90.9%, ≥CR of 42.6%, VGPR of 28.6% and PFS was not reached till study end point. Furthermore, the DR due to AEs for DaraVMP was also lesser (4.9%). Various trials [Table 2] are being conducted to establish correlation of frailty scores with parameters of efficacy. Conclusion: Management of frail and elderly NDMM patients is challenging as there is need to individualize therapy for this group. Novel agents such as lenalidomide, bortezomib and daratumumab have shown promising efficacy when used as combination therapies with other conventional agents. Intensity of treatment and efficacy goals should be tailored to the functional capacity and tolerance of each individual patient. There is need for focused clinical trials for this group in terms of greater recruitment into clinical trials to establish better correlation between frailty status and efficacy, and consolidating evidence for improved patient care. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.